Alzheimer's disease (AD)is the most common neurodegenerative disorder, and disproportionately affects the elderly. In America, it is estimated that the annual costs of caring for individuals with Alzheimer's disease are at least $100billion dollars. By the year 2050, it is estimated that there will be 14 million persons over the age of 65 affected with AD. The National Cell Repository for Alzheimer's Disease (NCRAD) was established 15 years ago to collect and maintain information and biological specimens on large numbers of genetically informative, phenotypically well-characterized families, having multiple individuals affected with AD. The goal of NCRAD during the past 15 years has been to ensure that researchers have access to the types of families and samples needed to address critical research questions. These families have been instrumental in dissecting the genetics of AD and have led to the publication of over 100 manuscripts. Initial efforts were focused on the recruitment of early onset, autosomal dominant families. Subsequently, NCRAD focused on the identification of kindreds with familial-non AD dementia. Most recently, there has been a large NIA sponsored genetics initiative to expand the collection of families with late onset AD. While the important role of apolipoprotein E (APOE) has been delineated in families with late onset AD, it is apparent that other genes must also contribute to disease susceptibility. This application proposes to provide the clinical and biological resources critical to AD researchers that will allow the elucidation of susceptibility genes for AD as well as other types of familial dementia. To achieve this goal, the following specific aims are proposed: 1) To work with the Alzheimer Disease Centers (ADCs) and national and local support groups to augment and maintain extensive clinical, neuropathological and biological material from multiplex AD and familial dementia kindreds. 2) To work with the ADCs to augment and maintain extensive clinical and biological material from a series of control individuals. 3) To widely promote and distribute samples maintained at NCRAD to qualified Alzheimer's disease investigators. Lay Summary: Alzheimer's disease (AD)is the most common degenerative disorder and causes enormous hardship for affected individuals and their families. This application seeks to continue a national resource of DNA and cell lines from individuals with AD and their family members so that researchers can use these samples to find genes that cause AD.